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1.PI3Kδ selectiveinhibitorwith a broad safety window

Yang, Qingshan et al. Clinical cancer research. (2015): 1537-42.

1) As a important member of PI3K/mTOR pathway which regulating cell proliferation and cell cycle, PI3Kδ is involved in early signaling responses of leukocytes in a wide variety of stimulations.

2) PI3Kδ is only expressed in hematopoietic lineage, which remains a broad safety window for PI3Kδ selective inhibitor comparing to pan-PI3K inhibitors or PI3Kα/β selective inhibitors.

3) High expression of PI3Kδ is found in Hematologic malignancies patients.

2.A high selective inhibition of PI3Kδin kinase and cellular level.

1) Asset against PI3Kδ increased by 16 times at kinase levels and by 2-14 times at cellular levels comparing with Idelalisib.

3.Excellent anti-B cell activity and good safety in vivo.

1) Inhibition of asset on rat activated B cell were 4-fold (1 h) and 15-fold (8 h) higher than that of Idelalisib, respectively, with less toxic than Idelalisib at the same dose in a 28-day repeated-dose toxicity test in rats.

2) hERG assay indicated the low risk of prolongation of QT interval and hERG block potency.

3) No genotoxicity observed in preclinical toxicity study. No abnormality observed in cardiovascular and respiratory system when administration in species of SD Rats and Beagle Dogs.

4.Clinical trial date: suitforQD and a better AUC. (higher AUC than Idelalisib at a much lower dose)

1）t_1/2= 16.4 h at a dose of 25 mg, which is suitable for QD.

2）At the same dose, asset in human showed a much higher AUC than Idelalisib.

Research progress：

High selective PI3Kδ inhibitoron phase 1 trial;

No genotoxicity and no cardiovascular and respiratory system abnormality was observed in pre-clinical study;

Good AUC was shown in clinic trial.